CASE PRESENTATION: A 33-year-old Palestinian woman born to consanguineous parents presented with a lifelong history of recurrent severe respiratory infections, growth failure (short stature and microcephaly), recurrent nephrolithiasis, chronic vomiting, generalized hirsutism, and bilateral hallux valgus. Laboratory evaluation revealed marked hypogammaglobulinemia (IgG <320 mg/dL, IgA <25 mg/dL, IgM <25 mg/dL), microcytic anemia, and severe vitamin D deficiency. Imaging confirmed chronic pulmonary small-airway changes and a chronically small right kidney with recurrent stones. Whole-exome sequencing identified a homozygous pathogenic SLC29A3 variant (c.1309G>A; p.Gly437Arg), establishing a diagnosis within the SLC29A3-related disorder spectrum. This case is unique due to its adult presentation, the exceptional severity of the humoral immunodeficiency, and the associated renal manifestations, which are infrequently reported in this spectrum.